Variant 5-134607038-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 4P and 3B. PM1PM2BP4_ModerateBP6

The NM_016103.4(SAR1B):c.509C>T(p.Ala170Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SAR1B
NM_016103.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.00

Variant links:

Genes affected

SAR1B (HGNC:10535): (secretion associated Ras related GTPase 1B) The protein encoded by this gene is a small GTPase that acts as a homodimer. The encoded protein is activated by the guanine nucleotide exchange factor PREB and is involved in protein transport from the endoplasmic reticulum to the Golgi. This protein is part of the COPII coat complex. Defects in this gene are a cause of chylomicron retention disease (CMRD), also known as Anderson disease (ANDD). Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Mar 2010]

SAR1B links:

SAR1B (HGNC:):

SAR1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM1

In a chain GTP-binding protein SAR1b (size 197) in uniprot entity SAR1B_HUMAN there are 11 pathogenic changes around while only 1 benign (92%) in NM_016103.4

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23276177).

BP6

Variant 5-134607038-G-A is Benign according to our data. Variant chr5-134607038-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAR1B	NM_016103.4 linkuse as main transcript	c.509C>T	p.Ala170Val	missense_variant	7/7	ENST00000402673.7	NP_057187.1	Q9Y6B6
SAR1B	NM_001033503.3 linkuse as main transcript	c.509C>T	p.Ala170Val	missense_variant	8/8		NP_001028675.1	Q9Y6B6
SAR1B	XM_047417257.1 linkuse as main transcript	c.509C>T	p.Ala170Val	missense_variant	7/7		XP_047273213.1
SAR1B	XM_047417258.1 linkuse as main transcript	c.305C>T	p.Ala102Val	missense_variant	5/5		XP_047273214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAR1B	ENST00000402673.7 linkuse as main transcript	c.509C>T	p.Ala170Val	missense_variant	7/7	1	NM_016103.4	ENSP00000385432.2		Q9Y6B6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461422

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727050

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 24, 2024

The c.509C>T (p.A170V) alteration is located in exon 8 (coding exon 6) of the SAR1B gene. This alteration results from a C to T substitution at nucleotide position 509, causing the alanine (A) at amino acid position 170 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.28

DEOGEN2

Benign

0.098

T;.;.;T;.;T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

0.14

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

.;.;.;D;D;D;D

M_CAP

Benign

0.0074

MetaRNN

Benign

0.23

T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

L;.;.;L;.;.;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.49

N;N;N;N;N;N;N

REVEL

Benign

0.14

Sift

Benign

1.0

T;T;T;T;T;T;T

Sift4G

Benign

0.29

T;T;T;T;T;.;D

Polyphen

0.0

B;.;.;B;.;.;.

Vest4

0.28

MVP

0.75

MPC

0.21

ClinPred

0.45

GERP RS

5.8

Varity_R

0.10

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over